Mass spectrometry is an indispensable technique for the analysis of biologically important compounds. Thus, the development of techniques for mass spectrometric determinations of large, labile, polar molecules is of great importance to progress in the biomedical, biochemical, and biological sciences. Our general objective is to expand the utility of organic mass spectrometry in biochemical, biomedical, and biological sciences generally and in endocrinological research on hypophysiotropic hormones particularly. Our specific aims are as follows: i) to investigate the physical and chemical processes that govern the ejection of secondary ions from liquid and solid matrices that are subjected to bomdardment by particles with energies ranging from 5-50 keV, and ii) to evolve one or more methods capable of detecting less than or equal to 1 pmole of individual oligopeptides without unduly sacrificing the qualitative specificity of the mass spectrometry. The usefulness of mass spectrometry is reduced when samples cannot be analyzed due to bounds on mass range, sensitivity, or compound types. Current mass spectrometric sensitivities are particularly restrictive in research, such as that on hormones or molecular markers for diseases, where the availability of analyte is severely limited by requirements for sampling in vivo. Ionization techniques discovered during the last decade have greatly increased the variety and size of molecules amenable to mass spectrometric analysis; it has been noted, however, that comparable gains in sensitivity at the highest, ionizable molecular weights (10,000-20,000 daltons) will be required before full advantage can be taken of these new ion sources. The extent to which sensitivity can be increased without unduly sacrificing qualitative specificity is a matter for basic and applied research. The program of investigation described in this proposal would not only make general contributions to our understanding of desorption ionization processes, but it would utilize that valuable body of knowledge to bring about a significant reduction in mass spectrometric detection limits for hypophysiotropic hormones, an accomplishment that would markedly expand the horizons of research in endocrinology.